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Acute leukaemia in bcr/abl transgenic mice

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Abstract

THE Philadelphia chromosome, widely implicated in human leukaemia, is the result of a reciprocal translocation t(9;22) (q34;q11) in which the abl oncogene located at 9q34 is translocated to chromosome 22q11, where it is fused head-to-tail with 5" exons of the bcr gene1–8. In acute lymphoblastic leukaemia, some patients have a breakpoint within the major breakpoint cluster region of the bcr gene, whereas others have the break within its first intron6,9–13. This second type of translocation results in the transcription of a 7.0-kilobase chimaeric bcr/abl messenger RNA translated into a bcr/abl fusion protein, p190, which has an abnormal tyrosine kinase activity and is strongly autophosphorylated in vitro14. We have generated mice transgenic for a bcr/abl p190 DNA construct and find that progeny are either moribund with, or die of acute leukaemia (myeloid or lymphoid) 10–58 days after birth. This finding is evidence for a causal relationship between the Philadelphia chromosome and human leukaemia.

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Author notes

  1. John Groffen: To whom correspondence should be addressed.

Authors and Affiliations

  1. Section of Molecular Diagnosis, Department of Pathology, Children's Hospital of Los Angeles, 4650 Sunset Boulevard, Los Angeles, California, 90027, USA

    Nora Heisterkamp, Guido Jenster, Joanne ten Hoeve & John Groffen

  2. Section of Hematopathology, Department of Pathology, Children's Hospital of Los Angeles, 4650 Sunset Boulevard, Los Angeles, California, 90027, USA

    Daniel Zovich & Paul K. Pattengale

Authors
  1. Nora Heisterkamp
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  2. Guido Jenster
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  3. Joanne ten Hoeve
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  4. Daniel Zovich
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  5. Paul K. Pattengale
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  6. John Groffen
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Heisterkamp, N., Jenster, G., ten Hoeve, J. et al. Acute leukaemia in bcr/abl transgenic mice. Nature 344, 251–253 (1990). https://doi.org/10.1038/344251a0

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  • DOI: https://doi.org/10.1038/344251a0

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